title: The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer.
abstract: Celecoxib has shown potential anticancer activity against most carcinomas, especially in patients with familial adenomatous polyposis and precancerous disease of the colon. However, serious side effects of celecoxib restrict its generalized use for cancer therapy. In order to resolve these issues and develop an alternative strategy/preliminary approach, chitosan modified hydroxyapatite nanocarriers-mediated celecoxib delivery represents a viable strategy. We characterized the nanoparticle for morphology, particle size, zeta potential, crystalinity, functional group analysis, entrapment efficiency, drug release and hemocompatibility. The effects of celecoxib-loaded nanoparticles on colon cancer cell proliferation, morphology, cytoskeleton, cellular uptake and apoptosis were analysed in vitro. Further, we evaluated the antiproliferative, apoptotic and tumor inhibitory efficacy of celecoxib-loaded nanocarriers in a nude mouse human xenograft model. Nanoparticles exhibited small, narrow hydrodynamic size distributions, hemocompatibility, high entrapment efficiencies and sustained release profiles. In vitro studies showed significant antiproliferation, apoptosis and time-dependent cytoplasmic uptake of celecoxib-loaded Hap-Cht nanoparticles in HCT 15 and HT 29 colon cancer cells. Additional in vivo studies demonstrated significantly greater inhibition of tumor growth following treatment with this modified nanoparticle system. The present study indicates a promising, effective and safe means of using celecoxib, and potentially other therapeutic agents for colon cancer therapy.
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, India.
authors.forename: P
authors.initials: P
authors.lastname: Venkatesan
authors.forename: Nagaprasad
authors.initials: N
authors.lastname: Puvvada
authors.forename: Rupesh
authors.initials: R
authors.lastname: Dash
authors.forename: B N
authors.initials: BN
authors.lastname: Prashanth Kumar
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Belal
authors.initials: B
authors.lastname: Azab
authors.forename: Amita
authors.initials: A
authors.lastname: Pathak
authors.forename: Subhas C
authors.initials: SC
authors.lastname: Kundu
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
authors.forename: Mahitosh
authors.initials: M
authors.lastname: Mandal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D011720:Pyrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D013449:Sulfonamides; D048271:Chitosan; D017886:Durapatite; D000068579:Celecoxib